Method and apparatus for storing and dispensing reagent beads

ABSTRACT

Embodiments of the invention provide an efficient and effective technique for storing and dispensing reagent beads. In some embodiments, an apparatus is provided for dispensing reagent beads contained in a bead storage device which includes a bead carrier having a plurality of wells; a plurality of reagent beads disposed in the wells; and a cover tape releasably attached to the bead carrier to cover the wells and retain the reagent beads in the wells. The apparatus comprises a channel in which to place the bead storage device with the bead carrier facing a support wall of the channel and the cover tape facing a stripping wall of the channel. The stripping wall includes a stripping gap disposed between a stripping edge and an opposite edge, and a dispense opening provided adjacent the opposite edge on a side of the stripping wall opposite from the stripping edge. The cover tape is insertable through the stripping gap to be pulled against the stripping edge to peel the cover tape from the bead carrier to move the wells of the bead carrier inside the channel toward the dispense opening and expose the wells individually to dispense the reagent beads.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 13/849,640, filed Mar. 25, 2013, which is continuation of U.S.application Ser. No. 12/512,926 filed Jul. 30, 2009, now U.S. Pat. No.8,409,531, issued Apr. 2, 2013, which is a continuation of U.S.application Ser. No. 11/146,304, filed Jun. 6, 2005, now U.S. Pat. No.7,575,721, issued Aug. 9, 2009 all of which are hereby incorporated byreference in their entirety.

BACKGROUND OF THE INVENTION

This application relates generally to systems and methods for storingand dispensing reagent beads for use in analyzing a sample.

Many types of chemical reactions, such as nucleic acid amplificationreactions, are important for research, medical, and industrialapplications. Such reactions are used in clinical and biologicalresearch, detection and monitoring of infectious diseases, detection ofmutations, detection of cancer markers, environmental monitoring,genetic identification, detection of pathogens in biodefenseapplications, and the like, e.g., Schweitzer et al., Current Opinion inBiotechnology, 12: 21-27 (2001); Koch, Nature Reviews Drug Discovery, 3:749-761 (2004). In particular, polymerase chain reactions (PCRs) havefound applications in all of these areas, including applications forviral and bacterial detection, viral load monitoring, detection of rareand/or difficult-to-culture pathogens, rapid detection of bio-terrorthreats, detection of minimal residual disease in cancer patients, foodpathogen testing, blood supply screening, and the like, e.g., Mackay,Clin. Microbiol. Infect., 10: 190-212 (2004); Bernard et al., ClinicalChemistry, 48: 1178-1185 (2002). In regard to PCR, key reasons for suchwidespread use are its speed and ease of use (typically performed withina few hours using standardized kits and relatively simple and low costinstruments), its sensitivity (often a few tens of copies of a targetsequence in a sample can be detected), and its robustness (poor qualitysamples or preserved samples, such as forensic samples or fixed tissuesamples are readily analyzed), Strachan and Read, Human MolecularGenetics 2 (John Wiley & Sons, New York, 1999).

Reagent beads carrying a reagent are commonly used to provide thereagent for analyzing samples including, for example, analysis bynucleic acid amplification reactions such as PCR. In addition to nucleicacid amplification reactions, reagent beads may be used in a widevariety of other chemical reaction/detection methods known in the art.Reagent beads are fragile and contain static charges that present statichandling problems.

BRIEF SUMMARY OF THE INVENTION

Embodiments of the present invention provide an efficient and effectivetechnique for storing and dispensing reagent beads.

In accordance with an aspect of the present invention, a device forstoring and dispensing reagent beads comprises a bead carrier includinga plurality of wells; a plurality of reagent beads disposed in theplurality of wells; and a cover tape releasably attached to the beadcarrier to cover the plurality of wells and retain the plurality ofreagent beads in the plurality of wells of the bead carrier. The beadcarrier and the cover tape each comprise an anti-static material. Thecover tape is peelable from the bead carrier to expose the plurality ofwells individually to dispense the plurality of reagent beads from theplurality of wells.

In some embodiments, the anti-static material comprises styreneimpregnated with carbon. In specific embodiments, the cover tape isreleasably attached to the bead carrier by a pressure sensitiveadhesive. Alternatively, the cover tape may be heat-sealed to the beadcarrier. The bead carrier preferably includes a linear array of wellsspaced by a generally uniform distance. The cover tape is peelable fromthe bead carrier to expose the plurality of wells individually one at atime. Preferably, at least a portion of each well is transparent.

Another aspect of the present invention is directed to an apparatus fordispensing reagent beads contained in a bead storage device whichincludes a bead carrier having a plurality of wells; a plurality ofreagent beads disposed in the plurality of wells; and a cover tapereleasably attached to the bead carrier to cover the plurality of wellsand retain the plurality of reagent beads in the plurality of wells ofthe bead carrier. The apparatus comprises a channel in which to placethe bead storage device with the bead carrier facing a support wall ofthe channel and the cover tape facing a stripping wall of the channel.The stripping wall includes a stripping gap disposed between a strippingedge and an opposite edge, and a dispense opening provided adjacent theopposite edge on a side of the stripping wall opposite from thestripping edge. The cover tape is insertable through the stripping gapto be pulled against the stripping edge to peel the cover tape from thebead carrier to move the plurality of wells of the bead carrier insidethe channel toward the dispense opening and expose the plurality ofwells individually to dispense the plurality of reagent beads from theplurality of wells through the dispense opening.

In some embodiments, the stripping wall includes a spout coupled to thedispense opening and being oriented generally downward to dispense thereagent beads by gravity. A counter is coupled to a portion of the covertape which has been peeled from the bead carrier to count the number ofwells being exposed to dispense the reagent beads based on a travelamount of the cover tape with respect to the stripping edge.

Another aspect of the invention is directed to an apparatus fordispensing reagent beads contained in a bead storage device whichincludes a bead carrier having a plurality of wells; a plurality ofreagent beads disposed in the plurality of wells; and a cover tapereleasably attached to the bead carrier to cover the plurality of wellsand retain the plurality of reagent beads in the plurality of wells ofthe bead carrier. The apparatus comprises a housing having in aninterior thereof a channel in which to place the bead storage devicewith the bead carrier facing a support wall of the channel and the covertape facing a stripping wall of the channel, wherein the stripping wallincludes a stripping gap disposed between a stripping edge and anopposite edge, and a dispense opening provided adjacent the oppositeedge on a side of the stripping wall opposite from the stripping edge; aclutch configured to pull a leading end of the cover tape insertedthrough the stripping gap to pull the cover tape against the strippingedge; and a wheel coupled to the clutch for turning the clutch to pullthe cover tape.

In some embodiments, the clutch includes a ratchet mechanism to permitone-directional pulling of the cover tape. The wheel is exposed from theinterior of the housing and sized to be rotatable by a user's finger orthumb. The stripping wall includes a spout coupled to the dispenseopening and being oriented generally downward to dispense the reagentbeads by gravity. The stripping edge includes a bend which bends outwardfrom the channel and backward away from the opposite edge to guide thecover tape. The channel is generally circular in shape. The clutch isconfigured to pull the leading end of the cover tape inserted throughthe stripping gap against the stripping edge to peel the cover tape fromthe bead carrier to move the plurality of wells of the bead carrierinside the channel toward the dispense opening and expose the pluralityof wells individually one at a time to dispense the reagent beads fromthe plurality of wells through the dispense opening. The wheel isconfigured to turn by at least about 60° to move from one well to a nextwell toward the dispense opening and expose the next well to dispensethrough the dispense opening. A counter is coupled to the clutch tocount the number of wells being exposed to dispense the reagent beadsbased on a travel amount of the cover tape.

Another aspect of the present invention is directed to a method ofdispensing reagent beads contained in a bead storage device whichincludes a bead carrier having a plurality of wells; a plurality ofreagent beads disposed in the plurality of wells; and a cover tapereleasably attached to the bead carrier to cover the plurality of wellsand retain the plurality of reagent beads in the plurality of wells ofthe bead carrier. The method comprises placing the bead storage devicein a channel with the bead carrier facing a support wall of the channeland the cover tape facing a stripping wall of the channel, wherein thestripping wall includes a stripping gap disposed between a strippingedge and an opposite edge, and a dispense opening provided adjacent theopposite edge on a side of the stripping wall opposite from thestripping edge. The method further comprises inserting the cover tapethrough the stripping gap; and pulling the cover tape against thestripping edge to peel the cover tape from the bead carrier to move theplurality of wells of the bead carrier inside the channel toward thedispense opening and expose the plurality of wells individually todispense the plurality of reagent beads from the plurality of wellsthrough the dispense opening.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exploded elevational view of a reagent bead storage deviceaccording to an embodiment of the present invention.

FIG. 2 is a perspective view of a bead dispensing apparatus according toan embodiment of the present invention.

FIG. 3 is an elevational of the bead dispensing apparatus of FIG. 2 fordispensing reagent beads from the reagent bead storage device of FIG. 1.

FIG. 4 is an exploded perspective view of a bead dispensing apparatusaccording to another embodiment of the present invention.

FIG. 5 is a perspective view showing the interior of the bead dispensingapparatus of FIG. 4.

FIG. 6 is an elevational view of the bead dispensing apparatus of FIG.4.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 is an exploded view of a reagent bead storage device for storingreagent beads to be dispensed. The storage device 10 includes a beadcarrier 12 having a plurality of wells 14 and a plurality of reagentbeads 16 disposed in the wells 14. The bead carrier 12 may be a flexibletape having the wells 14 formed therein, or the bead carrier may be arigid or flexible molded part. FIG. 1 shows one bead 16 in each well 14,but the number of beads may vary in other embodiments. A cover tape 20is releasably attached to the bead carrier 12 to cover the wells 14 andretain the reagent beads 16 in the wells 14 of the bead carrier 12. Thebead carrier 12 and the cover tape 20 are made of an anti-staticmaterial. The cover tape 20 is peelable from the bead carrier 12 toexpose the wells 14 individually to dispense the reagent beads 16 fromthe wells 14, as described in more detail below.

An example of a suitable anti-static material is styrene impregnatedwith carbon. Of course, other anti-static materials may be used.Examples of other anti-static materials includes, without limitation,metals and treated plastics (e.g., plastics impregnated with aconductive metal or plastics given a surface treatment). The cover tape20 may be releasably attached to the bead carrier 12 by a pressuresensitive adhesive, or heat-sealed to the bead carrier 12. The covertape is preferably peelable from the bead carrier using a manual forceexerted by one or more fingers of the user. In FIG. 1, the bead carrierincludes a linear array of wells 14 spaced by a generally uniformdistance. The cover tape 20 is peelable from the bead carrier 12 toexpose the plurality of wells 14 individually one at a time. Otherarrangements or configurations are possible, including nonlineararrangement of wells and nonuniform distances between wells. At least aportion of each well 14 is preferably transparent to allow one to seethe content inside.

FIGS. 2 and 3 show a bead dispensing apparatus according to anembodiment of the present invention. The dispensing apparatus 30 can beused to dispense reagent beads 16 contained in the bead storage device10 of FIG. 1. The dispensing apparatus 30 includes a channel 32 in whichto place the bead storage device 10 with the bead carrier 12 facing asupport wall 34 of the channel 32 and the cover tape 20 facing astripping wall 36 of the channel 32. The stripping wall 36 includes astripping gap 40 disposed between a stripping edge 42 and an oppositeedge 44. A dispense opening 48 is provided adjacent the opposite edge 44on a side of the stripping wall 36 opposite from the stripping edge 42.The cover tape 20 is insertable through the stripping gap 40 to bepulled against the stripping edge 42 to peel the cover tape 20 from thebead carrier 12, thereby moving the wells 14 of the bead carrier 12inside the channel 32 toward the dispense opening 48 and exposing thewells 14 individually to dispense the reagent beads 16 from the wells 14through the dispense opening 48. The stripping wall 36 desirablyincludes a spout 50 coupled to the dispense opening 48 which is orientedgenerally downward to dispense the reagent beads 16 by gravity.

As seen in FIG. 3, the cover tape 20 is pulled against the strippingedge 42 in a direction generally opposite from a direction of travel ofthe bead carrier 12 toward the dispense opening 48. The generallyopposite direction of pulling is convenient, but not required toseparate the cover tape 20 from the bead carrier 12. Other directionscan work. The pulling of the cover tape 20 creates the driving force forseparating the cover tape 20 from the bead carrier 12 and for moving thebead carrier 12 toward the dispense opening 48 to dispense the reagentbeads 16 from the wells 14 through the dispense opening 48. A counter 60may be coupled to a portion of the cover tape 20 which has been peeledfrom the bead carrier 12 to count the number of wells 14 being exposedto dispense the reagent beads 16 based on a travel amount of the covertape 20 with respect to the stripping edge 42. This is more easily doneif the distance between the wells 14 is uniform. In an alternativeembodiment, a counter may be coupled to a portion of the bead carrier 12which has been separated from the cover tape 20 to count the number ofexposed wells 14.

FIG. 4 is an exploded perspective view of a bead dispensing apparatusaccording to another embodiment of the present invention. The dispensingapparatus 100 includes a base 102 and a cover 104 which are connected toform a housing with an interior. The base 102 includes in the interiorthereof a channel 110 in which to place the bead storage device 10 withthe bead carrier 12 facing a support wall 112 of the channel 110 and thecover tape 20 facing a stripping wall 114 of the channel 110. Thestripping wall 114 includes a stripping gap 120 disposed between astripping edge 122 and an opposite edge 124, and a dispense opening 128provided adjacent the opposite edge 124 on a side of the stripping wall114 opposite from the stripping edge 122. In the embodiment shown, thestripping edge 122 includes a bend which bends outward from the channel110 and backward away from the opposite edge 124 to guide the cover tape20. The channel 110 is generally circular in shape. A spout 130 isdesirably coupled to the dispense opening 128 and to be orientedgenerally downward to dispense the reagent beads 16 by gravity. Theapparatus optionally includes a spout cap 131 for covering the spout 130when the bead dispenser is not in use. FIG. 4 shows a desiccant 136which may be placed inside the housing.

A shaft 140 is provided in the base 102 to support a clutch 150 which isconfigured to grip and pull a leading end of the cover tape 20 insertedthrough the stripping gap 120 to pull the cover tape 20 against thestripping edge 122. A wheel 152 is coupled to the clutch 150 for turningthe clutch 150 to pull the cover tape 20. The wheel 152 may include acorrugated surface for easier turning by the finger of a user. Theclutch 150 preferably includes a ratchet mechanism to permitone-directional pulling of the cover tape 20. The ratchet mechanism mayinclude a gear and a pawl. As seen in FIGS. 5 and 6, the wheel 152 ispreferably exposed from the interior of the housing and sized to berotatable by a user's finger or thumb.

As seen in FIG. 5, the clutch 150 is configured to pull the leading endof the cover tape 20 inserted through the stripping gap 120 against thestripping edge 122 to peel the cover tape 20 from the bead carrier 12 tomove the wells 14 of the bead carrier 12 inside the channel 110 towardthe dispense opening 128 with the spout 130 and expose the wells 14individually one at a time to dispense the reagent beads 16 from thewells 14 through the dispense opening 128 and the spout 130. To avoidaccidentally dispensing beads, the wheel 152 is preferably configured toturn by a preset angle to move from one well to a next well toward thedispense opening 128 and expose the next well to dispense through thedispense opening 128 and spout 130. For example, the preset angle ispreferably at least about 60°, and more preferably about 90-120°. Acounter may optionally be coupled to the clutch 150 which is connectedto a portion of the cover tape 20 that has been peeled from the beadcarrier 12 to count the number of wells 14 being exposed to dispense thereagent beads 16 based on a travel amount of the cover tape 20 (aspulled by turning the clutch). In some embodiments, the housing of theapparatus 100 is transparent and has numbers 1 to X printed around itscircumference, where X is the number of wells 14, to permit a user tosee how many filled wells 14 remain by simple visual inspection.

FIG. 6 shows one example of dispensing beads by turning the wheel 152 bya user's finger to pull the cover tape. The spout 130 is orientedgenerally downward the dispense the beads 16 by gravity. In otherembodiments, pulling of the cover tape can be performed by a machineeither automatically or under the control of a user.

It is to be understood that the above description is intended to beillustrative and not restrictive. Many embodiments will be apparent tothose of skill in the art upon reviewing the above description. Thescope of the invention should, therefore, be determined not withreference to the above description, but instead should be determinedwith reference to the appended claims alone with their full scope ofequivalents.

1-20. (canceled)
 21. An apparatus for dispensing reagent beads containedin the device of claim 1, the apparatus comprising: a housing enclosingthe device and the clutch, with the cover tape facing a stripping wallof the housing, wherein the stripping wall is a continuous wall having afirst end (a stripping edge) and a second end (an opposite edge), whichare located in a close proximity to each other defining a stripping gapbetween the stripping edge and the opposite edge, and a dispense openingprovided adjacent the opposite edge on a side of the stripping wallopposite from the stripping edge, the leading end of the cover tape isinserted through the stripping gap, wherein the clutch is configured topull the leading end of the cover tape against the stripping edge topeel the cover tape from the bead carrier to move the plurality of wellsof the bead carrier toward the dispense opening and expose the pluralityof wells individually to dispense the plurality of reagent beads fromthe plurality of wells through the dispense opening.
 22. The apparatusof claim 21, wherein the dispense opening is oriented generally downwardand coupled to a spout to dispense the reagent beads by gravity.
 23. Theapparatus of claim 21, wherein the stripping edge includes a bendextending outward and backward away from the opposite edge to guide thecover tape.
 24. The apparatus of claim 21, wherein the housing furthercomprises a support wall and a channel disposed between the support walland the stripping wall.
 25. The apparatus of claim 21, wherein the covertape is insertable through the stripping gap to be pulled against thestripping edge to peel the cover tape from the bead carrier to move theplurality of wells of the bead carrier toward the dispense opening andexpose the plurality of wells individually one at a time to dispense thereagent beads through the dispense opening.
 26. The apparatus of claim21, wherein the clutch includes a ratchet mechanism to permitone-directional pulling of the cover tape.
 27. The apparatus of claim21, further comprising a wheel coupled to the clutch for turning theclutch to pull the cover tape.
 28. The apparatus of claim 21, furthercomprising a counter coupled to a portion of the cover tape which hasbeen peeled from the bead carrier to count the number of wells beingexposed to dispense the reagent beads based on a travel amount of thecover tape with respect to the stripping edge.
 29. The apparatus ofclaim 27, wherein the wheel is configured to turn by at least about 60°to move from one well to a next well toward the dispense opening andexpose the next well to dispense the reagent bead through the dispenseopening.
 30. The apparatus of claim 21, further comprising a countercoupled to the clutch to count the number of wells being exposed todispense the reagent beads based on a travel amount of the cover tape.31. The apparatus of claim 21, wherein the clutch is directly connectedto the leading end of the cover tape.
 32. A method of dispensing reagentbeads contained in the apparatus of claim 21, the method comprising:pulling the leading end of the cover tape by the clutch against thestripping edge to peel the cover tape from the bead carrier to move theplurality of wells of the bead carrier toward the dispense opening andexpose the plurality of wells individually to dispense the plurality ofreagent beads from the plurality of wells through the dispense opening.33. The method of claim 32, wherein the cover tape is pulled against thestripping edge in a direction generally opposite from a direction oftravel of the bead carrier toward the dispense opening.
 34. The methodof claim 32, further comprising orienting the dispense opening generallydownward with respect to the wells to dispense the reagent beads bygravity.
 35. The method of claim 32, wherein the cover tape is pulledagainst the stripping edge to peel the cover tape from the bead carrierto move the plurality of wells of the bead carrier toward the dispenseopening and expose the plurality of wells individually one at a time todispense the reagent beads from the plurality of wells through thedispense opening.
 36. The method of claim 35, further comprisingcounting the number of wells being exposed to dispense the reagent beadsbased on a travel amount of the cover tape with respect to the strippingedge.
 37. The method of claim 32, wherein the clutch includes a ratchetmechanism to permit one-directional pulling of the cover tape.
 38. Themethod of claim 32, wherein pulling the cover tape comprises turning awheel coupled to the clutch.
 39. The method of claim 32, wherein theclutch is directly connected to the leading end of the cover tape.